4.7 Review

Lenacapavir: A novel injectable HIV-1 capsid inhibitor

Related references

Note: Only part of the references are listed.
Article Infectious Diseases

Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals

Alex Durand Nka et al.

Summary: The study evaluated the genetic variability of HIV-1 capsid and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades. The overall prevalence of lenacapavir DRMs was low, supporting its effectiveness for treatment and prevention.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2023)

Article Immunology

The HIV-1 Capsid-Targeted Inhibitor GSK878 Alters Selection of Target Sites for HIV DNA Integration

Kaitlin A. Marquis et al.

Summary: Despite the development of highly effective antiviral agents to treat HIV, the virus has developed resistance to these inhibitors, necessitating the development of new inhibitor classes. The HIV capsid has emerged as a promising target, and potent inhibitors can disrupt its function. This study compares the effects of two inhibitors on the integration targeting of HIV, revealing new insights into the role of the capsid and the consequences of inhibiting it.

AIDS RESEARCH AND HUMAN RETROVIRUSES (2023)

Article Infectious Diseases

Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study

Nicolas Margot et al.

Summary: Through in vitro and clinical assays, this study found that mutations in HIV-1 capsid protein are associated with increased resistance to Lenacapavir, but also decreased replication capacity of the mutant viruses. In the clinical trial, all participants who received Lenacapavir treatment showed a robust virological response without any detected resistance mutations.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2022)

Editorial Material Medicine, General & Internal

Lenacapavir effective in multidrug-resistant HIV infections

Susanne Krome

DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT (2022)

Article Virology

Drug Interactions in Lenacapavir-Based Long-Acting Antiviral Combinations

Maria E. Cilento et al.

Summary: Long-acting anti-HIV regimens have the potential to improve patients' quality of life by increasing dosing intervals. The combination therapy of lenacapavir with islatravir, rilpivirine, or cabotegravir shows additive inhibition in an HIV-1 reporter cell line. This study emphasizes the importance of effective drug combinations in long-acting regimens.

VIRUSES-BASEL (2022)

Article Multidisciplinary Sciences

Proactive strategies to optimize engagement of Black, Hispanic/Latinx, transgender, and nonbinary individuals in a trial of a novel agent for HIV pre-exposure prophylaxis (PrEP)

Michelle Cespedes et al.

Summary: This study aims to address the issue of underrepresentation of Black and Hispanic/Latinx cisgender men, transgender women, transgender men, and gender nonbinary individuals in HIV pre-exposure prophylaxis (PrEP) clinical trials. Strategic approaches were undertaken, including evidence-informed recommendations, engagement with stakeholders, and the establishment of a Global Community Advisory and Accountability Group (GCAG).

PLOS ONE (2022)

Article Immunology

Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir

Nicolas A. Margot et al.

Summary: Addition of lenacapavir to optimized background regimen resulted in significant viral suppression in highly treatment-experienced people with multidrug-resistant HIV. However, the unintentional use of lenacapavir as monotherapy led to the development of resistance.

JOURNAL OF INFECTIOUS DISEASES (2022)

Article Microbiology

Structural and Mechanistic Bases of Viral Resistance to HIV-1 Capsid Inhibitor Lenacapavir

Stephanie M. Bester et al.

Summary: In this study, the researchers investigated the drug resistance of HIV-1 to Lenacapavir. They found that the Q67H and N74D mutations reduced the binding affinity of the inhibitor, and proposed a modification to increase its potency.
Article Multidisciplinary Sciences

Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection

Guochao Wei et al.

Summary: This study highlights the importance of prion-like low complexity domains in binding and increasing the avidity when interacting with viral capsid, through structural, biochemical, and virological assays.

NATURE COMMUNICATIONS (2022)

Article Medicine, General & Internal

Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection

Sorana Segal-Maurer et al.

Summary: Patients with multidrug-resistant HIV-1 infection showed greater reduction in viral load when treated with lenacapavir compared to placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Article Microbiology

Absence of Lenacapavir (GS-6207) Phenotypic Resistance in HIV Gag Cleavage Site Mutants and in Isolates with Resistance to Existing Drug Classes

Nicolas Margot et al.

Summary: LEN is a potent inhibitor of HIV-1 capsid and has shown strong antiviral response in mutants with Gag cleavage site mutations and resistance to other drug classes. While LEN demonstrated wild-type susceptibility, reduced susceptibility was observed for control drugs.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Review Virology

The Role of Capsid in the Early Steps of HIV-1 Infection: New Insights into the Core of the Matter

Nawal AlBurtamani et al.

Summary: This review highlights the significant advances in understanding the role of the HIV-1 capsid in the virus life cycle and its potential as a pharmacological target for inhibiting HIV-1 replication. It also discusses promising small molecules, some in clinical trials, as potential targets for HIV-1 therapy.

VIRUSES-BASEL (2021)

Review Virology

The Viral Capsid: A Master Key to Access the Host Nucleus

Guillermo Blanco-Rodriguez et al.

Summary: Viruses have evolved strategies to manipulate the cellular machinery in order to replicate their genetic material and gain access to the host nucleus. They utilize the nuclear pore complex to enter the nucleus and replicate, with each virus employing unique tactics to achieve this goal. These viruses all require capsid remodeling to interact with the nuclear import machinery.

VIRUSES-BASEL (2021)

Article Infectious Diseases

Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients

Anne-Genevieve Marcelin et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2020)

Article Medicine, General & Internal

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection

Michael Kozal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Multidisciplinary Sciences

Clinical targeting of HIV capsid protein with a long-acting small molecule

John O. Link et al.

NATURE (2020)

Review Infectious Diseases

Antibody-based strategies in HIV therapy

Wesley D. Kufel

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2020)

Article Multidisciplinary Sciences

Structural and mechanistic bases for a potent HIV-1 capsid inhibitor

Stephanie M. Bester et al.

SCIENCE (2020)

Review Microbiology

Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug- Resistant HIV-1 Infection

Mario V. Beccari et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

Article Immunology

Trends in HIV-1 Drug Resistance Mutations from a US Reference Laboratory from 2006 to 2017

Ron M. Kagan et al.

AIDS RESEARCH AND HUMAN RETROVIRUSES (2019)

Article Microbiology

Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration

Vasudevan Achuthan et al.

CELL HOST & MICROBE (2018)

Article Medicine, General & Internal

Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1

Brinda Emu et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Review Microbiology

HIV-1 capsid: the multifaceted key player in HIV-1 infection

Edward M. Campbell et al.

NATURE REVIEWS MICROBIOLOGY (2015)

Article Microbiology

Extreme Genetic Fragility of the HIV-1 Capsid

Suzannah J. Rihn et al.

PLOS PATHOGENS (2013)